5-23510049-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020227.4(PRDM9):c.301+44del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (5407 hom., cov: 0)
  • Exomes 𝑓: 0.33 (648 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRDM9 NM_020227.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47

Genes affected

PRDM9 (HGNC:13994): (PR/SET domain 9) The protein encoded by this gene is a zinc finger protein with histone methyltransferase activity that catalyzes histone H3 lysine 4 trimethylation (H3K4me3) during meiotic prophase. This protein contains multiple domains, including a Kruppel-associated box (KRAB) domain, an SSX repression domain (SSXRD), a PRD1-BF1 and RIZ homologous region, a subclass of SET (PR/SET) domain, and a tandem array of C2H2 zinc fingers. The zinc finger array recognizes a short sequence motif, leading to local H3K4me3, and meiotic recombination hotspot activity. The observed allelic variation alters the DNA-binding sequence specificity of the protein, resulting in distinct meiotic recombination hotspots amongst individuals and populations. Multiple alternate alleles of this gene have been described. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-23510049-AT-A is Benign according to our data. Variant chr5-23510049-AT-A is described in ClinVar as [Benign]. Clinvar id is 1249566.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM9	NM_020227.4	c.301+44del		intron_variant		ENST00000296682.4
PRDM9	NM_001376900.1	c.301+44del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM9	ENST00000296682.4	c.301+44del		intron_variant		1	NM_020227.4	P1
PRDM9	ENST00000502755.6	c.301+44del		intron_variant		4
PRDM9	ENST00000635252.1	c.124+44del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.354 AC: 37408 AN: 105682 Hom.: 5401 Cov.: 0

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.211

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.332

GnomAD3 exomes AF: 0.256 AC: 24687 AN: 96360 Hom.: 24 AF XY: 0.252 AC XY: 12886 AN XY: 51080

Gnomad AFR exome AF: 0.278

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.247

Gnomad EAS exome AF: 0.288

Gnomad SAS exome AF: 0.273

Gnomad FIN exome AF: 0.214

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.276

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.326 AC: 366281 AN: 1122686 Hom.: 648 Cov.: 0 AF XY: 0.325 AC XY: 181923 AN XY: 560120

Gnomad4 AFR exome AF: 0.360

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.354 AC: 37414 AN: 105674 Hom.: 5407 Cov.: 0 AF XY: 0.349 AC XY: 17230 AN XY: 49318

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.333

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34033521; hg19: chr5-23510158;